Objective: The objective of this study is to examine the natural course of infectious and inflammatory diseases of the nervous system, to identify causative or associated pathogens when unknown, and generally to better understand the underlying immunological, genetic and pathophysiologic mechanisms that cause and contribute to these diseases and their ultimate neurological outcomes. Study Population: The study population will be patients at least 2 years old with known or suspected infection or inflammation of the nervous system and family members. Participants will be recruited through referrals to the NIH. Design: This is a longitudinal case series with standardized research data collection at predefined time points. Participants will have scheduled visits at the NIH either as an outpatient or an inpatient. The core research evaluations include: a comprehensive history and neurological examination; blood collection; neuroimaging; and lumbar puncture. Follow up visits will be individualized based on clinical needs and results of research evaluations. For some participants, no additional NIH visits will be necessary. Additionally, we will also enroll participants with known or suspected infections or inflammation of the nervous system from whom only biological samples collected by outside clinicians will be processed and retained for research analyses. In cases were samples remain from those collected for clinical reasons and the samples are deidentified, the samples may be obtained with a waiver of informed consent. Outcome Measures: The study outcomes will primarily be the characterizations of varied inflammatory and infectious nervous system diseases. These characterizations will include: the clinical phenotype and biomarkers.
- INCLUSION CRITERIA: At the time of enrollment, participants will: 1. Have a known or suspected infection or inflammation of the nervous system or post infection sequelae based on clinical or imaging data provided by the referral facility. For the purpose of this study, neuroinfectious disease or neuroinflammation is defined as any of the following: 1. fever with nervous system signs or symptoms (excluding delirium) 2. any neurological symptoms accompanied by cerebrospinal fluid (CSF) with evidence of inflammation (which may include pleocytosis, hypoglycorrachia, elevated protein, or other evidence of intrathecal immune activation including IgG index or presence of oligoclonal bands) 3. systemic infection or inflammatory disease with neurological involvement 4. neuroimaging suggestive of infection or inflammation (for example, presence of contrast-enhancing lesions on CT or MRI) 5. clinical presentation suggestive of infection or inflammatory process of the nervous system without better explanation 6. history of infection or inflammatory process of the nervous system 2. Be willing to participate in the protocol s procedures, unless clinically contraindicated 3. Be willing to provide informed consent, either directly or via appointed legally authorized representative 4. Be willing to consent for collection of clinical data or biological samples or their cryopreservation 5. Be at least 2 years old INCLUSION CRITERIA FOR PROCESSING OF BIOLOGICAL SAMPLES ONLY: At the time of enrollment, participants will: 1. Have a known or suspected infection or inflammation of the nervous system or post infection sequelae based on clinical or imaging data provided by the referral facility. For the purpose of this study, neuroinfectious disease or neuroinflammation is defined as any of the following: 1. fever with nervous system signs or symptoms (excluding delirium) 2. any neurological symptoms accompanied by cerebrospinal fluid (CSF) with evidence of inflammation (which may include pleocytosis, hypoglycorrachia, elevated protein, or other evidence of intrathecal immune activation including IgG index or presence of oligoclonal bands) 3. systemic infection or inflammatory disease with neurological involvement 4. neuroimaging suggestive of infection or inflammation (for example, presence of contrast-enhancing lesions on CT or MRI) 5. clinical presentation suggestive of infection or inflammatory process of the nervous system without better explanation 6. history of infection or inflammatory process of nervous system. 2. Be willing to provide informed consent, either directly or via appointed legally authorized representative 3. Be willing to consent for collection of clinical data or biological samples or their cryopreservation 4. Be at least 2 years old EXCLUSION CRITERIA: At the time of enrollment, participants will: 1. Not have a clinically significant medical condition that, in the best judgment of the investigators, may expose the patient to undue risk of harm or prevent the patient from completing the study (examples include, but are not limited to, ischemic cardiomyopathy, clotting disorder, brittle diabetes) 2. Not have an acute or unstable medical condition that, in the best judgement of the investigator, would be difficult to handle at the NIH Clinical Center 3. Not have a clearly-established diagnosis of well-characterized disease entity with validated treatment algorithms for which proposed resource investment, in the opinion of the investigators, would not contribute to further advancement of knowledge EXCLUSION CRITERIA FOR PROCESSING OF BIOLOGICAL SAMPLES ONLY: At the time of enrollment, participants will not have: 1. A clearly-established diagnosis of well-characterized disease entity with validated treatment algorithms for which proposed resource investment, in the opinion of the investigators, would not contribute to further advancement of knowledge INCLUSION CRITERIA FOR FAMILY MEMBERS: 1. Have a family member enrolled on 15-N-0125 2. Be at least 2 years old 3. Be able to provide informed consent and comply with study procedures EXCLUSION CRITERIA FOR FAMILY MEMBERS: 1. Not willing to consent for collection of biological samples or their cryopreservation